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Histamine H 2 receptors mediate the inhibitory effect of histamine on human eosinophil degranulation
Author(s) -
Ezeamuzie Charles I,
Philips Elizabeth
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703556
Subject(s) - dimaprit , mepyramine , histamine , medicine , thioperamide , histamine h2 receptor , chemistry , endocrinology , cimetidine , pharmacology , agonist , histamine receptor , receptor , antagonist , biology , biochemistry
The effect of histamine on human eosinophil degranulation and the receptor mediating such effect were studied in vitro using the complement C5a‐mediated eosinophil peroxidase (EPO) release model. Following pre‐treatment with 5 μg ml −1 cytochalasin B(CB), C5a induced a concentration‐dependent release of EPO from eosinophils isolated from healthy donors. Histamine (0.1–50 μ M ), but not L‐histidine, inhibited concentration‐dependently C5a‐induced EPO release with IC 50 (95% CI) of 0.6 μ M (0.3–1.2 μ M ) and maximal inhibition of ∼60%. A similar effect was seen with the selective H 2 agonists dimaprit (IC 50 (95% CI)=6.9 μ M (3.2–10.6 μ M )) and amthamine (IC 50 (95% CI)=0.4 μ M (0.2–0.7 μ M )). Neither the selective H 1 agonist 6‐(2‐(4‐imidazolyl)ethylamino)‐N‐(4‐trifluoromethylphenyl) heptanecarboxamide(HTMT), nor the selective H 3 agonists imetit (up to 100 μ M ) had any significant effect. The inhibition by histamine was reversed by cimetidine (0.1–30 μ M ) and other H 2 antagonists, but not the H 1 antagonist mepyramine (1.0–100 μ M ), nor the H 3 antagonist thioperamide (1.0–100 μ M ). Cimetidine (1–30 μ M ) shifted to the right the dimaprit log dose‐response curve, producing a pA 2 value of 5.9 and Schild's plot slope of 0.98, thus confirming simple competitive antagonism. Histamine (10–100 μ M ) increased intracellular level of adenosine 3′,5′‐cyclic monophosphate, which was completely abolished by cimetidine (30 μ M ), but not mepyramine or thioperamide. The cyclic AMP analogue – dibutyryl cyclic AMP – also inhibited degranulation (IC 50 ∼300 μ M ). The cyclic AMP phosphodiesterase(PDE) IV inhibitor rolipram (10 μ M ) synergistically enhanced the inhibition of EPO release by histamine. These results suggest that histamine, via stimulation of H 2 receptors and a consequent elevation of intracellular levels of cyclic AMP, inhibits human eosinophil degranulation.British Journal of Pharmacology (2000) 131 , 482–488; doi: 10.1038/sj.bjp.0703556